Cetuximab-resistant oral squamous cell carcinoma cells become sensitive in anchorage-independent culture conditions through the activation of the EGFR/AKT pathway.


:We have previously shown that growth of the oral squamous cell carcinoma cell line SAS, is resistant to cetuximab in monolayer culture conditions, even though epidermal growth factor receptor (EGFR) was phosphorylated, but the growth of SAS aggregates was sensitive to cetuximab. In the present study, we demonstrate differences in the EGFR signaling pathways utilized by SAS cells in monolayer and suspension cultures at the molecular level. Cetuximab treatment of SAS cells in monolayer cultures inhibits the phosphorylation of EGFR and ERK, and reduces the cell migratory potency, but not cell proliferation. AG1478 treatment reduces the phosphorylation of EGFR, ERK and AKT, and affects cell growth in monolayer cultures. The phosphorylation levels of EGFR and AKT are significantly higher in SAS cell aggregates compared to monolayer cultures. Treatment with cetuximab and AG1478 reduces the growth of SAS aggregates and eliminates the phosphorylation of EGFR and AKT. Furthermore, proliferation of SAS aggregates is also inhibited by LY294002 and MK2206, which are inhibitors of PI3K and AKT, respectively. In addition, treatment with the lipid raft disruptor filipin III reduced the phosphorylation levels of EGFR and Akt in SAS aggregates, but not in SAS monolayer culture. These results suggest the possibility that ligands in the serum stimulate the phosphorylation of EGFR localized in lipid rafts leading to PI3K-AKT activation, which results in the growth of SAS aggregates, therefore resulting in the sensitivity of SAS aggregates to cetuximab.


Int J Oncol


Ohnishi Y,Yasui H,Kakudo K,Nozaki M




Has Abstract


2015-12-01 00:00:00












  • The p53-positive phenotype of breast cancers.

    abstract::One hundred and eighty-one breast cancer specimens were analyzed for nuclear p53 staining by immunochemical methods. There were 123 fine-needle cytological specimens and 58 frozen tissue sections of surgical biopsies. The microscopic evaluation of the staining fitted with a 4 group classification. Ninety-one samples (...

    journal_title:International journal of oncology

    pub_type: 杂志文章


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  • Older versus younger patients with metastatic adenocarcinoma of the esophagus, gastroesophageal junction, and stomach: a pooled analysis of eight consecutive North Central Cancer Treatment Group (NCCTG) trials.

    abstract::Whether elderly patients with metastatic esophageal, gastroesophageal, and gastric cancer do as well with chemotherapy as their younger counterparts was investigated in this pooled analysis. In total, 367 patients from 8 consecutive, first-line trials were included: i) etoposide + cisplatin; ii) 5-fluorourucil + leuco...

    journal_title:International journal of oncology

    pub_type: 杂志文章


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    abstract::Breast cancer (BrC) is a major public health problem worldwide. The intra-tumoral heterogeneity and tumor cell plasticity importantly contribute to disease progression and treatment failure. However, the dynamic interactions between different tumor clones, as well as their contribution to tumor aggressiveness are stil...

    journal_title:International journal of oncology

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    journal_title:International journal of oncology

    pub_type: 杂志文章


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    journal_title:International journal of oncology

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    journal_title:International journal of oncology

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  • Increased level of cell-derived microparticles in the cyst fluids of odontogenic keratocysts.

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    journal_title:International journal of oncology

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    journal_title:International journal of oncology

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    journal_title:International journal of oncology

    pub_type: 杂志文章


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  • Immortalization and characterization of pleomorphic adenoma cells by transfection with the hTERT gene.

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    journal_title:International journal of oncology

    pub_type: 杂志文章


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  • Oncogenic role of p53 is suppressed by si-RNA bicistronic construct of uPA, uPAR and cathepsin-B in meningiomas both in vitro and in vivo.

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    journal_title:International journal of oncology

    pub_type: 杂志文章


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    abstract::Cell synchrony was induced in AGF cells by blocking of the cell cycle at GI-S boundary with high concentrations (2 mM) of thymidine for 11 h. Prolonged arrest of cells in GI-S (15 h-20 h) induced progressive and time dependent apoptosis. Early morphological changes in cellular and nuclear morphology (blebbing) were mo...

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  • Modulation of Raf/MEK/ERK kinase activity does not affect the chemoresistance profile of advanced prostate cancer cells.

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    pub_type: 杂志文章


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  • Upregulated expression of SAC3D1 is associated with progression in gastric cancer.

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    journal_title:International journal of oncology

    pub_type: 杂志文章


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    更新日期:2020-07-01 00:00:00

  • Additive effects of EGF and IL-1β regulate tumor cell migration and invasion in gastric adenocarcinoma via activation of ERK1/2.

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    journal_title:International journal of oncology

    pub_type: 杂志文章


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    更新日期:2014-07-01 00:00:00